Pneumonia and influenza, taken together, are a leading cause of hospitalization and death in the United States. Although it has been appreciated for more than 2 centuries that influenza predisposes the host to secondary bacterial infections, the incidence and etiology of influenza-associated pneumonia has never been comprehensively studied. Several epidemiologic trends are fueling a desire to gain better insight into interactions between viruses and bacteria in the pathogenesis of pneumonia. In studies employing comprehensive diagnostic methods, the incidence of co-infections in CAP appears to be at least 40%. For these reasons, the time is right to undertake prospective study of the role of co-infections in pneumonia in children using comprehensive and sensitive diagnostic assays. We propose to conduct a clinical study of the incidence and etiology of pneumonia in hospitalized children at Le Bonheur Children's Hospital in Memphis, Tennessee in association with St. Jude Children's Research Hospital. We will use this opportunity to answer some interesting and important scientific questions about co-infections in this population. The underlying hypothesis for our Proposed Studies is that co-infections result in poorer outcomes than single infections. We will test this hypothesis by prospectively collecting sociodemographic, microbiological, clinical, and genomics data to determine associations with clinical outcomes.